Potassium Carbonate → 3-{4-[3-(Biphenyl-4-yloxy)-propoxy]-3-methoxy-phenyl}-2-methoxy-propionic acid ethyl ester

HRID 459153Notes

Reaction equation

HRID 459153 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH:5]([O:16][CH3:17])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[C:9]([O:14][CH3:15])[CH:8]=1)[CH3:2].Br[CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C.O>[CH2:1]([O:3][C:4](=[O:18])[CH:5]([O:16][CH3:17])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:20][CH2:21][CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:26][CH:25]=2)=[C:9]([O:14][CH3:15])[CH:8]=1)[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 152334631,1'-Biphenyl, 4-(3-bromopropoxy)-HCID 588229863-(4-Hydroxy-3-methoxy-phenyl)-2-methoxy-propionic acid ethyl ester

Product 1

HCID 588226693-{4-[3-(Biphenyl-4-yloxy)-propoxy]-3-methoxy-phenyl}-2-methoxy-propionic acid ethyl esterYield 59.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 3-(4-hydroxy-3-methoxy-phenyl)-2-methoxy-propionic acid ethyl ester (Example 132, Step A) (0.080 g, 0.31 mmol) in acetonitrile (10 mL) was added 4-(3-bromo-propoxy)biphenyl (Example 132, Step D) (0.101 g, 0.35 mmol) and potassium carbonate (0.115 g, 0.945 mmol). The resulting suspension was stirred at 85° C. overnight. After cooling, the reaction mixture was diluted with ethyl acetate (10 mL), and water (10 mL) was added. The organic layer was washed with water (10 mL) and brine (10 mL), dried (MgSO4), and concentrated. The crude product was purified by silica gel column chromatography (silica gel, hexanes/ethyl acetate, 7:3) to produce 3-{4-[3-(biphenyl-4-yloxy)-propoxy]-3-methoxy-phenyl}-2-methoxy-propionic acid ethyl ester (0.086 g, 59%). 1H-NMR (200.15 MHz, CDCl3): δ 7.57–7.26 (m, 7H), 6.98 (d, 2H, J=8.6), 6.87–6.73 (m, 3H), 4.25–4.17 (m, 6H), 3.91 (dd, 1H, J=7.0, 5.6), 3.83 (s, 3H), 3.35 (s, 3H), 2.97–2.93 (m, 2H), 2.31 (qn, 2H, J=5.9), 1.24 (t, 3H, J=7.3).

Workup

  1. temperatureAfter cooling
  2. additionwas added
  3. washThe organic layer was washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel column chromatography (silica gel, hexanes/ethyl acetate, 7:3)

Sources & evidence

ORD record
ord-75281f50a40141ddbc3ccc52fc4b871f
Source dataset
uspto-grants-2007_03
Patent number
US07192982B2

Reaction notes

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